VITAMIN-B-6 DEFICIENCY ACCELERATES METABOLIC TURNOVER OF CYSTATHIONASE IN RAT-LIVER

Although most of cystathionase was found to exist as an inactive apoen zyme in the liver of vitamin B-6-deficient rats, the concentrations of the immunoreactive enzyme protein were virtually the same for control and vitamin B-6-deficient livers, Under vitamin B-6 deficiency, howev er, the rate of synthesis of cystathionase, measured by incorporation of labeled amino acid into the immunoprecipitated enzyme, was increase d severalfold due to an increased level of cystathionase mRNA, Western blot analysis of lysosomal proteins showed that the amount of cystath ionase in the lysosomes from the liver of vitamin B-6-deficient rats w as also increased severalfold, This observation suggests that lysosome s specifically recognize the apocystathionase for sequestration in pre ference to the holoenzyme, The present study provides the molecular ba sis for dual roles of vitamin B-6 in controlling the metabolic turnove r of cystathionase; it regulates synthesis of the enzyme by modulating the expression of cystathionase gene, and it regulates degradation of the enzyme by different susceptibilities of apo- and holoenzymes to l ysosomal proteolysis. (C) 1996 Academic Press, Inc.